This prospective study utilizes a well-characterized cohort to determine factors that (1) predict the onset of depression, (2) differentially predict morbidity based on evidence of sleep dysregulation in the family of origin, and (3) protect against depression in an at-risk cohort. prospective follow-up of at-risk individuals allows unambiguous assessment of factors that precede onset of major depression. There are currently no clear physiological predictors for development of mood disorders. EEG sleep measures are promising for several reasons: (a) they have reliably been found to be abnormal in patients with unipolar major depression when depressed and when in remission, (b) there is clear genetic influence on sleep physiology, and (c) there is a genetic component in unipolar depression. We have found that reduced REM latency and related sleep characteristics aggregate in families, are associated with higher familial loading for depression and potentially predict substantial morbidity, especially in relation to number of episodes and manifestation of affective syndromes. Reduced REM latency also appears to confer risk for onset of depression. Confirmation of this finding, using prospective follow-up, would identify individuals at th highest risk for depression. In the proposed project, we plan to test definitively the hypothesis that reduced REM latency confers risk for new onset depression, while developing a more complex model of factors that differentially influence the clinical course of unipolar depression. We have preliminary data that factors influencing morbidity operate differentially depending on sleep dysregulation in the proband. Finally, we plan to initiate a prospective study of factors that diminish risk for depression. Seven new families (2 depressed, 5 normal) will be recruited and studied in the sleep laboratory. Measures of self- esteem, family environment and functioning, parenting styles, and social support will be collected in the first year of the project and will be used to test hypotheses about protective factors. The cohort will consist of 350 individuals; parents and siblings of 21 reduced REM latency depressed probands, 26 nonreduced REM latency depressed probands and 20 normal control probands. Participants will have comprehensive data on EEG sleep, psychiatric history, episode history, treatment history, medical history, family history, negative thinking, dysfunctional attitudes, coping strategies, social attachment and social adjustment. All participants will be interviewed at yearly intervals for 3 years. Data to be collected include psychiatric history, medical history and life events for the preceding year. This prospective study is a cost-effective means of ascertaining factors that may be critical in the etiology of depression by taking advantage of a well-studied cohort.